The influence of acute dietary nitrate supplementation on endothelial resistance to ischemia reperfusion injury in postmenopausal women

Physiology 2023 (Harrogate, UK) (2023) Proc Physiol Soc 54, PCB008

Poster Communications: The influence of acute dietary nitrate supplementation on endothelial resistance to ischemia reperfusion injury in postmenopausal women

Jocelyn Delgado1, Jigar Gosalia1, Matthew Studinski1, Michael Flanagan1, Yasina Somani1, David Proctor1,

1The Pennsylvania State University University Park United States, 2University of Leeds Leeds United Kingdom, 3Penn State College of Medicine University Park United States,

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With postmenopausal women expected to reach a population of 1.2 billion by 2030, there is a great need for low-risk, non-estrogen therapies for cardiovascular disease prevention. Evidence suggests that relative to the early follicular phase, women in the late follicular phase are protected against endothelial ischemia-reperfusion (IR) injury when estradiol concentrations are highest.1,2 This suggests that the concurrent loss of estrogen following menopause may impair recovery from endothelial ischemia-reperfusion injury (ex. heart attack, bypass surgery).3 Consumption of beetroot juice and other nitrate-rich foods (celery, spinach, lettuce, etc.) is an effective non-pharmaceutical intervention to increase systemic bioavailability of the vasoprotective molecule, nitric oxide, through the exogenous nitrate-nitrite-nitric oxide pathway. The purpose of this randomized, placebo-controlled, double-blind crossover clinical trial was to determine if a single dose of dietary nitrate supplementation, in the form of beetroot juice, can improve endothelial resistance to IR injury in postmenopausal women at two distinct stages of menopause. We hypothesized that a single dose of nitrate-rich beetroot juice would improve endothelial resistance to IR injury to a greater extent in early- compared to late-postmenopausal women. Early- (1-6 years following their final menstrual period (FMP), n=12) and late- (>6 years FMP, n=12) postmenopausal women consumed a single dose of nitrate-rich (600 mg/140 mL) and nitrate-depleted (placebo, 0 mg/140mL) beetroot juice. Study visits were separated by a washout period of at least two weeks. Whole arm endothelial IR injury was induced by inflating a pneumatic cuff (250 mmHg) for 20 minutes followed by 15 minutes of reperfusion. Brachial artery flow-mediated dilation (FMD, duplex ultrasound) was measured at baseline, acutely (90 minutes post-juice consumption), 15-, and 30 minutes after IR injury for each drink. Analyses with general linear models (SPSS) revealed a significant (p<0.05) time*treatment interaction effect for FMD. Pairwise comparisons revealed that FMD was significantly lower 15-minutes post-IR in comparison to all other time points with nitrate-depleted beetroot juice (Early- FMDplacebo=2.553.48%, Late- FMDplacebo=1.322.06) and was lower than post-IR with nitrate-rich beetroot juice (Early- FMDnitrate=3.924.15%, Late- FMDnitrate=3.242.67%, p=0.014). There was no significant interaction effect of menopausal stage. These results suggest that a single dose of dietary nitrate supplementation is sufficient to increase endothelial resistance to whole-arm IR injury to a similar extent in women at both stages of postmenopause. Our observations emphasize the endothelial protective benefits of dietary nitrate supplementation for postmenopausal vascular health. 



Where applicable, experiments conform with Society ethical requirements.

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